We propose to continue studies of X chromosome inactivation, using multiple approaches to explore the molecular basis and genetic consequences thereof. We will: 1) Analyze the relationship between autosomes and X chromosomes in human triploid and trisomic embryonic cells and mouse fibroblasts heterozygous for an X autosome translocation. 2) Determine if the silent X in human fibroblasts can be reactivated by mutagens or DNA transfer. 3) Continue studies of cloned human DNA to reveal unique properties of the X chromosome that makes it susceptible to inactivation. Use X DNA hybridization probes to purify the Barr body. 4) Determine if some X loci escape inactivation by analysis of fibroblast clones from heterozygotes for X linked variants. 5) Examine the conservation of the mammalian X with respect to chromosomal localization of Tfm and PGK. 6) Explore the basis for the "fragile site" and if it is a hot spot for recombination. 7) Search for selective elimination of harmful genetic variants in pertinent tissues of the heterozygote, using G6PD phenotype as the marker.